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Background <p>Serum neurofilament light and heavy chains (sNfL and sNfH) have been assessed as neuronal markers for amyotrophic lateral sclerosis (ALS) and dementias. Whereas sNfL has robust literature, systematic studies on sNfH are lacking. Here, we aimed to assess the diagnostic value of sNfH in comparison to sNfL in a broad range of neurodegenerative disorders.</p> Methods <p>We measured with immunoassays sNfH and sNfL in patients recruited in the multicenter German Frontotemporal Lobar Degeneration (FTLD) Consortium (n = 340) and in a single-center German cohort (n = 290). We assessed the diagnostic accuracy of serum biomarkers for ALS and dementia subtypes and their relationship with cognitive impairment.</p> Results <p>sNfH and sNfL were significantly increased in ALS (n = 90) vs. controls (n = 109) and ALS mimics (n = 56, p &lt; 0.001), with sNfL showing higher discriminative accuracy (AUC = 0.94–0.95) than sNfH (AUC = 0.87–0.88). sNfH/sNfL ratio did not improve the diagnostic performance. Both markers were elevated in patients with dementia (n = 289) vs. controls (p &lt; 0.001). sNfL was higher in behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA) and Creutzfeldt-Jakob disease (CJD) than in Alzheimer’s disease (AD), whereas sNfH was similar in AD, PPA and bvFTD. sNfL, but not sNfH, was correlated with cognitive impairment at baseline&#xa0;and cognitive decline at follow-up&#xa0;in AD and bvFTD.</p> Conclusions <p>sNfH and sNfL are elevated in motoneuron and dementia disorders. sNfH showed good discriminative accuracy for ALS, which was slightly lower than that of sNfL. sNfL, but not sNfH, showed prognostic value for assessing&#xa0;cognitive decline&#xa0;in dementia.</p>

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Serum neurofilaments for motoneuron and dementia diseases: a German multicenter cohort study

  • 期刊论文

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  • 发表日期：

    2026年6月2日

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  • Lorenzo Barba,
  • Petra Steinacker,
  • Steffen Halbgebauer,
  • Patrick Oeckl,
  • Bernhard Landwehrmeyer,
  • Jochen Weishaupt,
  • Federico Verde,
  • Nicola Ticozzi,
  • Vincenzo Silani,
  • Johannes Levin,
  • Sonja Schönecker,
  • Johannes Kornhuber,
  • Johannes Prudlo,
  • Matthias L. Schroeter,
  • Klaus Fassbender,
  • Klaus Fliessbach,
  • Janine Diehl-Schmid,
  • Holger Jahn,
  • Martin Lauer,
  • Johannes Dorst,
  • Angela Rosenbohm,
  • Samir Abu-Rumeileh,
  • Sarah Anderl-Straub,
  • Marie Söntgerth,
  • Fabiola Böhm,
  • Jens Wiltfang,
  • Markus Otto

摘要

Background

Serum neurofilament light and heavy chains (sNfL and sNfH) have been assessed as neuronal markers for amyotrophic lateral sclerosis (ALS) and dementias. Whereas sNfL has robust literature, systematic studies on sNfH are lacking. Here, we aimed to assess the diagnostic value of sNfH in comparison to sNfL in a broad range of neurodegenerative disorders.

Methods

We measured with immunoassays sNfH and sNfL in patients recruited in the multicenter German Frontotemporal Lobar Degeneration (FTLD) Consortium (n = 340) and in a single-center German cohort (n = 290). We assessed the diagnostic accuracy of serum biomarkers for ALS and dementia subtypes and their relationship with cognitive impairment.

Results

sNfH and sNfL were significantly increased in ALS (n = 90) vs. controls (n = 109) and ALS mimics (n = 56, p < 0.001), with sNfL showing higher discriminative accuracy (AUC = 0.94–0.95) than sNfH (AUC = 0.87–0.88). sNfH/sNfL ratio did not improve the diagnostic performance. Both markers were elevated in patients with dementia (n = 289) vs. controls (p < 0.001). sNfL was higher in behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA) and Creutzfeldt-Jakob disease (CJD) than in Alzheimer’s disease (AD), whereas sNfH was similar in AD, PPA and bvFTD. sNfL, but not sNfH, was correlated with cognitive impairment at baseline and cognitive decline at follow-up in AD and bvFTD.

Conclusions

sNfH and sNfL are elevated in motoneuron and dementia disorders. sNfH showed good discriminative accuracy for ALS, which was slightly lower than that of sNfL. sNfL, but not sNfH, showed prognostic value for assessing cognitive decline in dementia.